PDF(Pubmed)
Abstract：
Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ.
摘要：
双膦酸盐（BPs）已成功用于治疗许多以骨密度代谢减少为特征的疾病，比如骨质疏松,或者骨组织的肿瘤破坏，如多发性骨髓瘤和骨转移。这些药物通过引起系统性破骨细胞耗竭发挥其治疗作用，反过来,负责减少骨吸收。不幸的是,除了他们的有益活动，BP还可以确定称为颌骨坏死（ONJ）的可怕副作用。通常认为破骨细胞不能处理发炎/坏死的骨代表了ONJ的主要生理病理学方面。原则上,能够引起破骨细胞产生局部重新激活的治疗策略可以抵消ONJ并促进其病变的愈合.使用维生素D3依赖性破骨细胞生成的实验模型，我们先前已经证明镁是破骨细胞分化的强大诱导剂。在这里我们展示，令人惊讶的是,唑来膦酸盐的存在大大增强了这种效果，选择我们的研究，因为它是最有效和最危险的BP。这一发现使我们能够假设镁可能在ONJ的局部治疗中起重要作用。
